FDA Grants Priority Review to Sunvozertinib for NSCLC With EGFR Exon 20 Insertion Mutations

FDA grants priority review to sunvozertinib for platinum-pretreated NSCLC with EGFR exon 20 insertions.

Priority review was granted by the FDA for sunvozertinib (DZD9008), an oral EGFR inhibitor, to treat patients with platinum-pretreated, locally advanced, or metastatic NSCLC with EGFR exon 20 insertion mutations detected by an FDA-approved test.¹

The NDA submission was supported by findings from the multinational phase 2 WU-KONG1 Part B trial (NCT03974022), which investigated sunvozertinib in patients with relapsed/refractory NSCLC harboring EGFR exon 20 insertion mutations. Data from the trial, which were presented at the 2024 ASCO Annual Meeting and had a cutoff date of March 22, 2024, showed that evaluable patients who received sunvozertinib at 300 mg once daily (n = 107) achieved a best overall response rate (ORR) of 53.3% (97.5% CI, 42.0%-64.3%) and a confirmed ORR of 44.9% (97.5% CI, 34.0%-56.1%).² Best responses included complete response (CR; 2.8%), confirmed CR (1.9%), partial response (PR; 50.5%), confirmed PR (43.0%), PR pending confirmation (3.7%) stable disease (36.4%), and progressive disease (7.5%). Three patients were not evaluable for response.

“Patients with [NSCLC with] EGFR [exon 20 insertion mutations] face a poor prognosis and limited treatment options,” Xiaolin Zhang, PhD, chief executive officer of Dizal, stated in a news release.¹ “Sunvozertinib’s priority review designation marks an important regulatory milestone in Dizal’s efforts to address unmet medical needs worldwide. The results from the WU-KONG1 Part B study are promising. If approved, sunvozertinib as a single oral drug would offer a convenient and safe treatment option with superior efficacy for [patients with] NSCLC with EGFR [exon 20 insertion mutations].”

WU-KONG1 Part B enrolled patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations confirmed in tumor tissue.² Patients needed to have an ECOG performance status of 0 or 1 and have received prior treatment with platinum-based chemotherapy.

Patients were randomly assigned 1:1 to receive sunvozertinib at 200 mg daily or 300 mg daily. At the interim analysis, 111 patients went on to receive continuous dosing of the agent at 300 mg daily until trial discontinuation criteria were met.

Independent review committee (IRC)–assessed ORR served as the trial’s primary end point. IRC-assessed duration of response (DOR) was a key secondary end point. Other secondary end points included investigator-assessed ORR and DOR.

The median DOR was not reached, and the 9-month DOR rate was 57%.

Investigators observed antitumor activity with sunvozertinib regardless of the receipt of prior therapy with amivantamab-vmjw [Rybrevant]. The best ORRs in patients with and without prior amivantamab exposure were 50% and 53.8%, respectively.

The most common grade 3 or higher treatment-related adverse effects (TRAEs) observed with the agent at the 300-mg dose included diarrhea (17.1%), increased blood creatinine phosphokinase levels (10.8%), anemia (3.6%), rash (3.6%), increased lipase levels (3.6%), decreased neutrophil counts (2.7%), hypokalemia (2.7%), decreased appetite (2.7%), and asthenia (2.7%). TRAEs led to dose reduction and treatment discontinuation in 36.0% and 6.3% of patients, respectively. Investigators noted that most of the common TRAEs were grade 1 or 2 in severity and clinically manageable. No TRAEs led to fatal outcomes.

Previously, in April 2024, the FDA granted breakthrough therapy designation to sunvozertinib for patients with treatment-naive NSCLC harboring an EGFR exon 20 insertion mutation.¹

Notably, in August 2023, the National Medical Products Administration of China granted accelerated approval to sunvozertinib for the treatment of patients with advanced NSCLC harboring EGFR exon 20 insertion mutations who have received prior treatment with platinum-based chemotherapy. This regulatory decision was supported by findings from the phase 2 WU-KONG6 trial (NCT05712902), which evaluated the agent in this patient population.

References

1. U.S. FDA granted priority review to Dizal’s sunvozertinib new drug application. News release. Dizal. January 7, 2025. Accessed January 7, 2025. https://www.dizalpharma.com/news/detail?id=84&search=&currentPage=1
2. Yang J CH, Doucet L, Wang M, et al. A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: primary analysis of WU-KONG1 study. J Clin Oncol. 2024;42(suppl 16)8513. doi:10.1200/JCO.2024.42.16_suppl.8513